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《Medical Journal of Chinese People's Liberation Army》 2011-10
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Effect of Toll-like receptor-4 and NF-κB on expression of matrix metalloprotease 9 induced by lipopolysaccharide in human airway epithelial cells

LI Ya-qing,XU Wu-lin,YAN Jian-ping,XIA Ying-jie,WANG Hong.Department of Respiratory Medicine,Zhejiang Provincial People's Hospital,Hangzhou 310014,China  
Objective To study the effects of toll-like receptor-4(TLR-4) and nuclear factor-κB(NF-κB) on the expression of matrix metalloprotease 9(MMP-9) induced by lipopolysaccharide(LPS) in human airway epithelial cells,and explore the influence of TLR-4 inhibitor TAK-242 on the expression of MMP-9.Methods In order to study the effects of LPS on MMP-9 expression,HBE4-E6/E7 cells were challenged for 24 hours by different concentrations of LPS(0,0.1,1,10,100 μg/L),or challenged for 0,8,12,16 and 24 hours by LPS at a concentration of 10 μg/L.HBE4-E6/E7 cells were pretreated for 30min with TAK-242(100μg/L) or PDTC(50mg/L),and challenged for 24h by LPS at 100 μg/L thereafter.The expression of MMP-9 mRNA was assessed by RT-PCR and of MMP-9 protein by Western blotting.MMP-9 activity was determined by gel zymography.The active NF-κB production was determined by electrophoretic mobility shift assay(EMSA).Results The expression of MMP-9 mRNA in HBE4-E6/E7 cells was induced by LPS in both dose-and time-dependent manner(P0.05).Both TAK-242 and PDTC significantly inhibited the expression of MMP-9 mRNA and protein(P0.05),down-regulated MMP-9 activity(P0.05),and significantly inhibited active NF-κB production induced by LPS(P0.05).Conclusion MMP-9 expression is induced by LPS in human airway epithelial cells via TLR-4/NF-κB signal pathway,which can be inhibited by TAK-242.
【Fund】: 浙江省医药卫生科学研究基金(No.2008B007)
【CateGory Index】: R563.9
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